ESTRR
MCID: EST007
MIFTS: 41

Estrogen Resistance (ESTRR)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Estrogen Resistance

MalaCards integrated aliases for Estrogen Resistance:

Name: Estrogen Resistance 57 72 29 6 39 70
Estrogen Resistance Syndrome 58 36 17
Estrogen Insensitivity 57 72
Estrr 57 72

Characteristics:

Orphanet epidemiological data:

58
estrogen resistance syndrome
Inheritance: Autosomal recessive;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
based on 2 reported patients, 1 male and 1 female (last curated august 2013)


HPO:

31
estrogen resistance:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases


Summaries for Estrogen Resistance

UniProtKB/Swiss-Prot : 72 Estrogen resistance: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.

MalaCards based summary : Estrogen Resistance, also known as estrogen resistance syndrome, is related to aromatase deficiency and breast cancer. An important gene associated with Estrogen Resistance is ESR1 (Estrogen Receptor 1), and among its related pathways/superpathways are Endocrine resistance and Prolactin signaling pathway. Affiliated tissues include breast, uterus and bone, and related phenotypes are osteopenia and increased circulating gonadotropin level

OMIM® : 57 Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994). (615363) (Updated 05-Apr-2021)

KEGG : 36 Estrogen resistance syndrome is a rare, genetic endocrine disease, characterized by estrogen-receptor (ESR) insensitivity to estrogens. A few patients who has mutations in ESR1 gene has been reported. An adult male who was tall and had incomplete epiphyseal closure, and a young woman with delayed puberty have been described.

Wikipedia : 73 Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen... more...

Related Diseases for Estrogen Resistance

Diseases related to Estrogen Resistance via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 aromatase deficiency 11.1
2 breast cancer 10.2
3 wilms tumor 1 9.9
4 estrogen-receptor positive breast cancer 9.9
5 amenorrhea 9.9
6 ovarian cyst 9.9
7 acanthosis nigricans 9.8
8 colorectal cancer 9.8
9 congenital heart defects, hamartomas of tongue, and polysyndactyly 9.8
10 lymphoma 9.8
11 squamous cell carcinoma 9.8
12 hypogonadism 9.8
13 hyperinsulinism 9.8
14 pulmonary tuberculosis 9.8
15 adenocarcinoma 9.8
16 bronchiolo-alveolar adenocarcinoma 9.8
17 lung disease 9.8
18 48,xyyy 9.8

Graphical network of the top 20 diseases related to Estrogen Resistance:



Diseases related to Estrogen Resistance

Symptoms & Phenotypes for Estrogen Resistance

Human phenotypes related to Estrogen Resistance:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteopenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000938
2 increased circulating gonadotropin level 58 31 hallmark (90%) Very frequent (99-80%) HP:0000837
3 osteoporosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000939
4 primary amenorrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0000786
5 enlarged polycystic ovaries 58 31 hallmark (90%) Very frequent (99-80%) HP:0008675
6 hypoplasia of the uterus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000013
7 breast hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003187
8 absence of secondary sex characteristics 58 31 hallmark (90%) Very frequent (99-80%) HP:0008187
9 overgrowth 58 31 hallmark (90%) Very frequent (99-80%) HP:0001548
10 absence of pubertal development 58 31 hallmark (90%) Very frequent (99-80%) HP:0008197
11 marked delay in bone age 58 31 hallmark (90%) Very frequent (99-80%) HP:0003799
12 delayed epiphyseal ossification 58 31 hallmark (90%) Very frequent (99-80%) HP:0002663
13 acne 58 31 frequent (33%) Frequent (79-30%) HP:0001061
14 glucose intolerance 58 31 frequent (33%) Frequent (79-30%) HP:0001952
15 hyperinsulinemia 58 31 frequent (33%) Frequent (79-30%) HP:0000842
16 acanthosis nigricans 58 31 frequent (33%) Frequent (79-30%) HP:0000956
17 episodic abdominal pain 58 31 frequent (33%) Frequent (79-30%) HP:0002574
18 elevated tissue non-specific alkaline phosphatase 58 31 frequent (33%) Frequent (79-30%) HP:0010679
19 coronary artery atherosclerosis 31 frequent (33%) HP:0001677
20 delayed skeletal maturation 31 HP:0002750
21 abnormality of the adrenal glands 58 Excluded (0%)
22 tall stature 58 Very frequent (99-80%)
23 coronary atherosclerosis 58 Frequent (79-30%)
24 abnormality of circulating hormone level 58 Very frequent (99-80%)
25 abnormal testosterone level 58 Excluded (0%)
26 abnormality of the pubic hair 58 Excluded (0%)
27 impaired glucose tolerance 31 HP:0040270

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal:
osteopenia
delayed bone age (in male and female patients)
low trabecular volumetric bone density (in male patient)
low cortical volumetric bone density (in male patient)

Growth Height:
continued growth into adulthood (in male and female patients)

Chest Breasts:
absent breast development
breast development unresponsive to oral estrogen

Skeletal Spine:
decreased bone mineral density of lumbar spine (in male patient)

Skin Nails Hair Skin:
acanthosis nigricans, axillary (in male patient)
severe facial acne (in female patient)

Genitourinary Internal Genitalia Female:
primary amenorrhea
small uterus
large multicystic ovaries

Cardiovascular Heart:
early atherosclerosis of coronary artery (in male patient)

Genitourinary External Genitalia Female:
tanner stage 4 pubic hair

Skeletal Limbs:
incomplete epiphyseal closures in adulthood (in male and female patients)

Endocrine Features:
elevated serum estradiol (in male and female patients)
elevated serum estrone (in male and female patients)
elevated serum follicle-stimulating hormone (in male and female patients)
elevated serum luteinizing hormone (in male and female patients)
hyperinsulinemia (in male patient)
more

Clinical features from OMIM®:

615363 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Estrogen Resistance according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.1 BCAR1 BCAR3
2 Decreased viability GR00055-A-2 9.1 BCAR1 BCAR3
3 Decreased viability GR00249-S 9.1 BCAR1
4 Decreased viability GR00381-A-1 9.1 BCAR3

Drugs & Therapeutics for Estrogen Resistance

Search Clinical Trials , NIH Clinical Center for Estrogen Resistance

Genetic Tests for Estrogen Resistance

Genetic tests related to Estrogen Resistance:

# Genetic test Affiliating Genes
1 Estrogen Resistance 29 ESR1

Anatomical Context for Estrogen Resistance

MalaCards organs/tissues related to Estrogen Resistance:

40
Breast, Uterus, Bone, Testes, Prostate, Colon, Skin

Publications for Estrogen Resistance

Articles related to Estrogen Resistance:

(show top 50) (show all 148)
# Title Authors PMID Year
1
Familial Multiplicity of Estrogen Insensitivity Associated With a Loss-of-Function ESR1 Mutation. 6 57 61
27754803 2017
2
Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant. 57 6 61
23841731 2013
3
Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. 6 57 61
8090165 1994
4
Effects of an estrogen receptor α variant. 57
24152274 2013
5
Impact on bone of an estrogen receptor-alpha gene loss of function mutation. 57
18505767 2008
6
Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man. 57
9396482 1997
7
Variant in BCAR4 gene correlated with the breast cancer susceptibility and mRNA expression of lncRNA BCAR4 in Chinese Han population. 61
33113070 2021
8
Comprehensive and Sequential Gene Expression Analysis of Bone Healing Process Following Er:YAG Laser Ablation. 61
33347788 2021
9
Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion. 61
33144694 2021
10
The crucial role of epigenetic regulation in breast cancer anti-estrogen resistance: Current findings and future perspectives. 61
33301860 2020
11
Estrogen Regulation of mTOR Signaling and Mitochondrial Function in Invasive Lobular Carcinoma Cell Lines Requires WNT4. 61
33053661 2020
12
Long non-coding RNA BCAR4 promotes liver cancer progression by regulating proliferation, migration and invasion. 61
32782595 2020
13
LncRNA BCAR4 promotes liver cancer progression by upregulating ANAPC11 expression through sponging miR‑1261. 61
32319544 2020
14
Cyclin E1 and cyclin E2 in ER+ breast cancer: prospects as biomarkers and therapeutic targets. 61
32061162 2020
15
LncRNA LINP1 confers tamoxifen resistance and negatively regulated by ER signaling in breast cancer. 61
31927036 2020
16
Investigating the role of BCAR4 in ovarian physiology and female fertility by genome editing in rabbit. 61
32193429 2020
17
High Expression of BCAR1 by Circulating Tumor Cells and Tumor Tissues Is Predictive of a Poor Prognosis of Early-Stage Lung Adenocarcinoma Potentially Due to Regulation of Epithelial-Mesenchymal Transition. 61
33334252 2020
18
miR-452 Reverses Abnormal Glycosylation Modification of ERα and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1. 61
32983995 2020
19
MicroRNA-126-5p downregulates BCAR3 expression to promote cell migration and invasion in endometriosis. 61
31233772 2019
20
Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer. 61
31090264 2019
21
Prognostic value of long non-coding RNA breast cancer anti-estrogen resistance 4 in human cancers: A meta-analysis. 61
31124974 2019
22
Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals. 61
30382472 2019
23
LncRNA BCAR4, targeting to miR-665/STAT3 signaling, maintains cancer stem cells stemness and promotes tumorigenicity in colorectal cancer. 61
30962766 2019
24
Long Non-Coding RNA BCAR4 Promotes Growth, Invasion and Tumorigenicity by Targeting miR-2276 to Upregulate MMP7 Expression in Glioma. 61
31849498 2019
25
Resistance Exercise Evokes Changes on Urinary Bladder Function and Morphology in Hypoestrogen Rats. 61
32063862 2019
26
The Value of LncRNA BCAR4 as a Prognostic Biomarker on Clinical Outcomes in Human Cancers. 61
31762809 2019
27
BCAR4 activates GLI2 signaling in prostate cancer to contribute to castration resistance. 61
30513511 2018
28
Early-Onset Complete Ovarian Failure and Lack of Puberty in a Woman With Mutated Estrogen Receptor β (ESR2). 61
30113650 2018
29
Molecular and disease association of gestational diabetes mellitus affected mother and placental datasets reveal a strong link between insulin growth factor (IGF) genes in amino acid transport pathway: A network biology approach. 61
30335885 2018
30
Key regulators of lipid metabolism drive endocrine resistance in invasive lobular breast cancer. 61
30180878 2018
31
Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer. 61
30089255 2018
32
Up-regulated BCAR4 contributes to proliferation and migration of cervical cancer cells. 61
29937186 2018
33
High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer. 61
29304771 2018
34
A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. 61
29221134 2017
35
LncRNA BCAR4 promotes colon cancer progression via activating Wnt/β-catenin signaling. 61
29190958 2017
36
LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. 61
28963395 2017
37
Release of HER2 repression of trefoil factor 3 (TFF3) expression mediates trastuzumab resistance in HER2+/ER+ mammary carcinoma. 61
29088778 2017
38
TGF-β Stimulation of EMT Programs Elicits Non-genomic ER-α Activity and Anti-estrogen Resistance in Breast Cancer Cells. 61
28955730 2017
39
Increased Expression of Long Non-Coding RNA BCAR4 Is Predictive of Poor Prognosis in Patients with Non-Small Cell Lung Cancer. 61
28077810 2017
40
Lack of interaction between ErbB2 and insulin receptor substrate signaling in breast cancer. 61
27765041 2016
41
Designer interface peptide grafts target estrogen receptor alpha dimerization. 61
27462021 2016
42
Beta protein 1 homeoprotein induces cell growth and estrogen-independent tumorigenesis by binding to the estrogen receptor in breast cancer. 61
27449292 2016
43
Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. 61
26857361 2016
44
Function of G-Protein-Coupled Estrogen Receptor-1 in Reproductive System Tumors. 61
27314054 2016
45
Aromatase Inhibitors in the Treatment of Short Stature. 61
26684331 2016
46
RNA-Seq-based transcriptome analysis of Korean rose bitterling (Rhodeus uyekii) exposed to synthetic estrogen 17-α-ethinylestradiol (EE2). 61
26112897 2015
47
A new class of small molecule estrogen receptor-alpha antagonists that overcome anti-estrogen resistance. 61
26575173 2015
48
Structural insights into tumor-specific chaperoning activity of gamma synuclein in protecting estrogen receptor alpha 36 and its role in tamoxifen resistance in breast cancer. 61
26299756 2015
49
Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis. 61
26515727 2015
50
Protein Tyrosine Kinase 6 Regulates UVB-Induced Signaling and Tumorigenesis in Mouse Skin. 61
25938342 2015

Variations for Estrogen Resistance

ClinVar genetic disease variations for Estrogen Resistance:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ESR1 NM_000125.3(ESR1):c.1125G>T (p.Gln375His) SNV Pathogenic 60557 rs397509428 GRCh37: 6:152332819-152332819
GRCh38: 6:152011684-152011684
2 ESR1 NM_001328100.2(ESR1):c.-51C>T SNV Pathogenic 16592 rs104893956 GRCh37: 6:152163748-152163748
GRCh38: 6:151842613-151842613
3 ESR1 NM_000125.3(ESR1):c.1181G>A (p.Arg394His) SNV Pathogenic/Likely pathogenic 430713 rs1131692059 GRCh37: 6:152332875-152332875
GRCh38: 6:152011740-152011740
4 ESR1 NM_001328100.2(ESR1):c.851-26059T>A SNV risk factor 587697 rs1562787582 GRCh37: 6:152420342-152420342
GRCh38: 6:152099207-152099207
5 TMEM59 NM_004872.5(TMEM59):c.*23G>A SNV risk factor 587698 rs776119905 GRCh37: 1:54497800-54497800
GRCh38: 1:54032127-54032127
6 CCDC170 NC_000006.12:g.151627231G>A SNV Likely pathogenic 155877 rs2046210 GRCh37: 6:151948366-151948366
GRCh38: 6:151627231-151627231
7 CCDC170 NM_025059.4(CCDC170):c.1810G>A (p.Val604Ile) SNV Likely pathogenic 155873 rs6929137 GRCh37: 6:151936677-151936677
GRCh38: 6:151615542-151615542
8 CCDC170 NM_025059.4(CCDC170):c.*68A>C SNV Uncertain significance 155874 rs3734805 GRCh37: 6:151939350-151939350
GRCh38: 6:151618215-151618215
9 CCDC170 NM_025059.4(CCDC170):c.*978A>G SNV Uncertain significance 155875 rs9383589 GRCh37: 6:151940260-151940260
GRCh38: 6:151619125-151619125
10 CCDC170 NC_000006.12:g.151625494T>A SNV Uncertain significance 155876 rs12665607 GRCh37: 6:151946629-151946629
GRCh38: 6:151625494-151625494
11 CCDC170 NC_000006.12:g.151630085A>G SNV Uncertain significance 155878 rs9397435 GRCh37: 6:151951220-151951220
GRCh38: 6:151630085-151630085
12 CCDC170 NM_025059.4(CCDC170):c.1710+1144T>G SNV Uncertain significance 155872 rs12662670 GRCh37: 6:151918856-151918856
GRCh38: 6:151597721-151597721
13 ESR1 NM_000125.3(ESR1):c.1091T>A (p.Val364Glu) SNV Uncertain significance 16593 rs121913044 GRCh37: 6:152265638-152265638
GRCh38: 6:151944503-151944503

UniProtKB/Swiss-Prot genetic disease variations for Estrogen Resistance:

72
# Symbol AA change Variation ID SNP ID
1 ESR1 p.Gln375His VAR_070072 rs397509428
2 ESR1 p.Arg394His VAR_078516 rs113169205

Expression for Estrogen Resistance

Search GEO for disease gene expression data for Estrogen Resistance.

Pathways for Estrogen Resistance

Pathways related to Estrogen Resistance according to KEGG:

36
# Name Kegg Source Accession
1 Endocrine resistance hsa01522
2 Prolactin signaling pathway hsa04917
3 Estrogen signaling pathway hsa04915

Pathways related to Estrogen Resistance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.13 BCAR3 BCAR1
2 10.04 ESR1 BCAR1

GO Terms for Estrogen Resistance

Biological processes related to Estrogen Resistance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin receptor signaling pathway GO:0008286 8.96 BCAR3 BCAR1
2 endothelin receptor signaling pathway GO:0086100 8.62 BCAR3 BCAR1

Sources for Estrogen Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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